Local disinfection for drug delivery system

ABSTRACT

Apparatus and a method are presented, including disinfecting a disinfection chamber that is defined between (i) a prefilled therapeutic substance reservoir and (ii) a sterile fluid path disposed within a therapeutic substance delivery device. The sterile fluid path includes a needle at an upstream end of the sterile fluid path and an injection assembly at a downstream end of the sterile fluid path. The disinfection occurs subsequently to the prefilled therapeutic substance reservoir being engaged with the therapeutic substance delivery device. Subsequently to disinfecting the disinfection chamber, the disinfection chamber and then the reservoir are penetrated with the needle. Other applications are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a Continuation of PCT/IL2018/051178 toBen-David, which published as WO 2019/087198 and:

(a) claims priority from U.S. Application No. 62/581,886 to Plaskin,filed Nov. 6, 2017, entitled, “Local disinfection for prefilled drugdelivery system,” and

(b) claims priority from and is a continuation-in-part of U.S.application Ser. No. 15/872,552 to Plaskin, filed Jan. 16, 2018,entitled, “Local disinfection for prefilled drug delivery system,” whichpublished as US 2019/0134295 to Plaskin and which claims priority fromU.S. Application No. 62/581,886 to Plaskin, filed Nov. 6, 2017.

Each of the above-referenced applications is assigned to the assignee ofthe present application and is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to delivery of a therapeuticsubstance to a subject, and more specifically to wearable drug deliverydevices utilizing therapeutic substance reservoirs.

BACKGROUND

Pumps are often used in the medical industry for delivering therapeuticsubstances, e.g., drugs, to subjects. Therapeutic substances such assaline solution, insulin, antibiotics, chemotherapy drugs, andbiosimilar drugs may all be delivered to a subject with medical pumps.Some medical pumps utilize therapeutic substance reservoirs that areprefilled by a pharmaceutical company. The medical pumps may bemanufactured in a controlled environment and subsequently sterilized,and the therapeutic substance reservoirs may be prefilled in a sterileenvironment. When engaging a medical pump with a prefilled therapeuticsubstance reservoir, bacteria or viruses may be introduced into theengagement site.

SUMMARY OF THE INVENTION

Apparatus, such as for example a wearable medical patch pump, isprovided for use with a prefilled therapeutic substance reservoir, suchthat after engaging the pump with the reservoir, the engagement sitebetween the pump and the reservoir is disinfected prior to fluidcommunication between the pump and the reservoir being established. Thepatch pump is designed such that engagement between the prefilledtherapeutic substance reservoir and the pump defines a closed chamberbetween the reservoir and a sterile fluid path within the pump, referredto hereinbelow as a disinfection chamber. After the pump and reservoirhave been engaged, the disinfection chamber is disinfected. Subsequentlya needle from within the pump penetrates through the disinfectionchamber and into the reservoir in order to establish fluid communicationbetween the pump and the reservoir. Fluid communication between thereservoir and the sterile fluid path is thereby established with reducedrisk of potentially harmful bacteria coming in to contact with thetherapeutic substance. Typically, the reservoir does not have to bedisinfected prior to engagement with the pump, e.g., by swabbing withalcohol, nor does engagement of the reservoir and the pump have to occurwhile the reservoir and the fluid path are contained within a sterileenvironment.

There is therefore provided, in accordance with some applications of thepresent invention, a method including:

disinfecting a disinfection chamber that is defined between (i) aprefilled therapeutic substance reservoir and (ii) a sterile fluid pathdisposed within a therapeutic substance delivery device,

-   -   the sterile fluid path including a needle at an upstream end of        the sterile fluid path and an injection assembly at a downstream        end of the sterile fluid path; and subsequently, penetrating the        disinfection chamber and then the reservoir with the needle.

For some applications, the step of disinfecting the disinfection chamberis performed following a user of the therapeutic substance deliverydevice engaging the prefilled therapeutic substance reservoir with thetherapeutic substance delivery device, the disinfection chamber beingdefined when the prefilled therapeutic substance reservoir becomesengaged with the therapeutic substance delivery device.

For some applications, the step of disinfecting the disinfection chamberis performed following a user of the therapeutic substance deliverydevice removing the therapeutic substance delivery device fromcommercial packaging, the prefilled therapeutic substance reservoir andthe therapeutic substance delivery device being engaged with one anotherinside the commercial packaging.

For some applications, disinfecting the disinfection chamber includesactivating a disinfection assembly and subsequently terminating theactivation of the disinfection assembly, and penetrating thedisinfection chamber includes penetrating the disinfection chamberwithin 10 seconds after terminating the activation of the disinfectionassembly.

For some applications, disinfecting the disinfection chamber includesactivating a disinfection assembly and terminating activation of thedisinfection assembly within 5 minutes after activating the disinfectionassembly.

For some applications, disinfecting the disinfection chamber includesirradiating the disinfection chamber with ultraviolet radiation.

For some applications, irradiating the disinfection chamber includesirradiating the disinfection chamber with ultraviolet radiation at apower level of 1-200 mW.

For some applications, irradiating the disinfection chamber includesirradiating the disinfection chamber with ultraviolet radiation at awavelength of 100-400 nm.

For some applications, irradiating the disinfection chamber with theultraviolet radiation includes irradiating the disinfection chamber withultraviolet radiation at a plurality of wavelengths.

For some applications, irradiating the disinfection chamber includesirradiating the disinfection chamber with ultraviolet light using anultraviolet light emitting diode.

For some applications, the method further includes:

subsequently to irradiating the disinfection chamber with theultraviolet light, measuring a value indicative of intensity of theultraviolet radiation within the disinfection chamber; and

terminating the irradiation of the disinfection chamber at a timedetermined based on the measured value.

For some applications, measuring the value indicative of intensity ofthe ultraviolet radiation includes measuring the intensity of theultraviolet radiation within the disinfection chamber using anultraviolet sensor disposed within the disinfection chamber.

For some applications, (a) irradiating the disinfection chamber withultraviolet radiation includes activating an ultraviolet light emittingdiode (UV LED) and (b) measuring the value indicative of intensity ofthe ultraviolet radiation includes measuring a current input to the UVLED.

For some applications, disinfecting the disinfection chamber includesheating the disinfection chamber.

For some applications, heating the disinfection chamber includes heatingthe disinfection chamber to a temperature of 40-70 degrees Celsius.

For some applications, heating the disinfection chamber includes heatingthe disinfection chamber to a temperature of 70-300 degrees Celsius.

For some applications, disinfecting the disinfection chamber includesreleasing a disinfectant fluid into the disinfection chamber.

For some applications, disinfecting the disinfection chamber includesdisinfecting the disinfection chamber within 5 minutes prior topenetrating the disinfection chamber and subsequently the reservoir withthe needle.

For some applications, disinfecting the disinfection chamber includesdisinfecting the disinfection chamber at least 1 month followingengagement of the prefilled therapeutic substance reservoir with thetherapeutic substance delivery device.

For some applications, disinfecting the disinfection chamber includesdisinfecting the disinfection chamber at least 6 months followingengagement of the prefilled therapeutic substance reservoir with thetherapeutic substance delivery device.

For some applications, the disinfecting of the disinfection chamber isat least a second disinfecting of the disinfection chamber, a firstdisinfecting of the disinfection chamber occurring prior to thetherapeutic substance delivery device being packaged for commercialsale.

For some applications, the method further includes disinfecting thedisinfection chamber at least one time between the first disinfecting ofthe disinfection chamber and the at least a second disinfecting of thedisinfection chamber.

There is further provided, in accordance with some applications of thepresent invention, apparatus for delivering a therapeutic substance to asubject, the apparatus including:

a therapeutic substance delivery device:

-   -   (a) including a sterile fluid path for delivering the        therapeutic substance to the subject, the sterile fluid path        including a needle at an upstream end of the sterile fluid path        and an injection assembly at a downstream end of the sterile        fluid path, and    -   (b) configured to engage with a prefilled therapeutic substance        reservoir, such that when the therapeutic substance delivery        device and the reservoir are engaged with one another a        disinfection chamber is defined between the sterile fluid path        and the reservoir, the needle being configured to penetrate the        disinfection chamber and subsequently the reservoir when the        therapeutic substance delivery device and the reservoir are        engaged with one another, such that fluid communication is        established between the reservoir and the sterile fluid path;

a disinfection assembly disposed within the therapeutic substancedelivery device and configured to disinfect the disinfection chamberprior to the needle penetrating the disinfection chamber; and

control circuitry configured to (a) activate the disinfection assembly,(b) terminate the activation of the disinfection assembly, andsubsequently (c) drive the needle to penetrate the disinfection chamberand subsequently the reservoir.

For some applications, the control circuitry is configured to terminatethe activation of the disinfection assembly within 5 minutes afteractivating the disinfection assembly.

For some applications, the control circuitry is configured to drive theneedle to penetrate the disinfection chamber within 10 seconds afterterminating the activation of the disinfection assembly.

For some applications, a surface area of the disinfection chamber is1-400 mm2.

For some applications, the disinfection assembly includes an ultravioletradiation source that is configured to emit ultraviolet radiation, andthe control circuitry is configured to activate the ultravioletradiation source to irradiate the disinfection chamber.

For some applications, the ultraviolet radiation source is configured toemit the ultraviolet radiation at a power level of 1-200 mW.

For some applications, the ultraviolet radiation source is configured toemit the ultraviolet radiation at a wavelength of 100-400 nm.

For some applications, the ultraviolet radiation source is configured toemit the ultraviolet radiation at a plurality of wavelengths.

For some applications, the ultraviolet radiation source includes anultraviolet light emitting diode.

For some applications, at least one surface of the disinfection chamberis a reflective surface configured to reflect the ultraviolet radiation.

For some applications, the reflective surface is configured to reflectat least 10% of the ultraviolet radiation.

For some applications, the reflective surface includes expandedpolytetrafluoroethylene (ePTFE).

For some applications, the reflective surface includes aluminum.

For some applications, the reflective surface of the disinfectionchamber is configured to focus the ultraviolet radiation to a designatedarea within the disinfection chamber, the designated area being within 3mm of where the needle penetrates the reservoir.

For some applications:

the apparatus further includes a sensor configured to measure a valueindicative of intensity of the ultraviolet radiation within thedisinfection chamber, and

the control circuitry is configured to (a) activate the ultravioletradiation source, (b) receive the value indicative of the intensity ofthe ultraviolet radiation, (c) terminate the activation of theultraviolet radiation source at a time determined based on the measuredvalue, and subsequently (d) drive the needle to penetrate thedisinfection chamber and subsequently the reservoir.

For some applications, the control circuitry is configured to (a)activate the ultraviolet radiation source, (b) measure a current inputto the ultraviolet radiation source, the current being indicative ofintensity of the ultraviolet radiation within the disinfection chamber,(c) terminate the activation of the ultraviolet radiation source at atime determined based on the measured current, and subsequently (d)drive the needle to penetrate the disinfection chamber and subsequentlythe reservoir.

For some applications, the ultraviolet radiation source includes anultraviolet light emitting diode (UV LED), and the control circuitry isconfigured to measure a current input to the UV LED.

For some applications, the disinfection assembly includes a heat sourceand the control circuitry is configured to activate the heat source toheat the disinfection chamber.

For some applications, the control circuitry is configured to activatethe heat source to heat the disinfection chamber to a temperature of40-70 degrees Celsius.

For some applications, the control circuitry is configured to activatethe heat source to heat the disinfection chamber to a temperature of70-300 degrees Celsius.

For some applications, the control circuitry is configured to (a)activate the heat source, (b) measure a current input to the heatsource, the current being indicative of temperature of the disinfectionchamber, (c) terminate the activation of the heat source at a timedetermined based on the measured current, and subsequently (d) drive theneedle to penetrate the disinfection chamber and then the reservoir.

For some applications:

the apparatus further includes a temperature sensor disposed within thedisinfection chamber and configured to measure a temperature of thedisinfection chamber, and

the control circuitry is configured to (a) activate the heat source, (b)receive a value from the temperature sensor of the temperature of thedisinfection chamber, (c) terminate the activation of the heat source ata time determined based on the measured temperature, and subsequently(d) drive the needle to penetrate the disinfection chamber and then thereservoir.

For some applications, the disinfection assembly includes a disinfectantfluid reservoir containing disinfectant fluid, and the control circuitryis configured to activate the disinfectant fluid assembly to release thedisinfectant fluid from the disinfectant fluid reservoir into thedisinfection chamber.

For some applications, the control circuitry is further configured toactivate the therapeutic substance delivery device to deliver thetherapeutic substance to the subject.

For some applications, the apparatus is packaged for commercial salewith the therapeutic substance delivery device and the reservoir engagedwith one another.

For some applications, the control circuitry is configured tosequentially (a) activate the disinfection assembly a first time priorto the apparatus being packaged for commercial sale, (b) terminate theactivation of the disinfection assembly, (c) activate the disinfectionassembly at least a second time at least 1 month following the apparatusbeing packaged for commercial sale, (d) terminate the activation of thedisinfection assembly, and (e) drive the needle to penetrate thedisinfection chamber and subsequently the reservoir.

For some applications, the control circuitry is configured to activatethe disinfection assembly the at least a second time at least 6 monthsfollowing the apparatus being packaged for commercial sale.

For some applications, the apparatus is packaged for commercial salewith the therapeutic substance delivery device and the prefilledtherapeutic substance reservoir, the therapeutic substance deliverydevice and the prefilled therapeutic substance reservoir not beingengaged with one another.

For some applications, the apparatus is packaged for commercial salewithout the prefilled therapeutic substance reservoir.

For some applications, the sterile fluid path is a first sterile fluidpath and the needle is a first needle, the therapeutic substancedelivery device:

-   -   (a) further including a second sterile fluid path, the second        sterile fluid path including a second needle at an upstream end        of the second sterile fluid path and the injection assembly at a        downstream end of the second fluid path,    -   (b) further configured to engage with a second prefilled        therapeutic substance reservoir, such that when the first and        second reservoirs are engaged with the therapeutic substance        delivery device first and second disinfection chambers are        defined respectively (i) between the first sterile fluid path        and the first reservoir, and (ii) between the second sterile        fluid path and the second reservoir,    -   (c) further including a first sterile fluid path valve disposed        between the first needle and the injection assembly and        configured to control fluid communication between the first        reservoir and the injection assembly, and    -   (d) further including a second sterile fluid path valve disposed        between the second needle and the injection assembly and        configured to control fluid communication between the second        reservoir and the injection assembly,

the first and second needles being configured to penetrate the first andsecond disinfection chambers respectively and subsequently the first andsecond reservoirs respectively when the therapeutic substance deliverydevice is engaged with the first and second reservoirs, such that afirst fluid communication is established between the first sterile fluidpath and the first reservoir and a second fluid communication isestablished between the second sterile fluid path and the secondreservoir, and

the disinfection assembly being configured to (a) disinfect the firstdisinfection chamber prior to the first needle penetrating the firstdisinfection chamber, and (b) disinfect the second disinfection chamberprior to the second needle penetrating the second disinfection chamber.

For some applications, the disinfection assembly is a first disinfectionassembly configured to disinfect the first disinfection chamber, theapparatus further includes a second disinfection assembly configured todisinfect the second disinfection chamber, and the control circuitry isconfigured to activate the first and second disinfection assemblies.

For some applications:

(a) the needle is a first needle and the sterile fluid path furtherincludes a second needle at the upstream end of the sterile fluid path,

(b) when the therapeutic substance delivery device and the reservoir areengaged with one another the first and second needles are configured topenetrate the disinfection chamber and subsequently the reservoir suchthat fluid communication is established between the reservoir and thesterile fluid path via the first and second needles, and

(c) the control circuitry is configured to drive the first and secondneedles to penetrate the disinfection chamber, within 10 seconds afterterminating the activation of the disinfection assembly.

The present invention will be more fully understood from the followingdetailed description of applications thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic illustration of a therapeutic substance deliverydevice that includes a disinfection assembly and is configured to engagewith a prefilled therapeutic substance reservoir, the reservoir beingshown outside the therapeutic substance delivery device, in accordancewith some applications of the present invention;

FIG. 1B is a schematic illustration of the therapeutic substancedelivery device of FIG. 1A with the prefilled therapeutic substancereservoir shown engaged with the therapeutic substance delivery device,in accordance with some applications of the present invention;

FIG. 1C is a schematic illustration of the therapeutic substancedelivery device of FIGS. 1A-B, showing establishment of fluidcommunication by penetration of the reservoir with a needle, inaccordance with some applications of the present invention;

FIG. 1D is a schematic illustration of a therapeutic substance deliverydevice that includes a disinfection assembly, showing a reflectivesurface within a disinfection chamber, in accordance with someapplications of the present invention;

FIG. 2A is a schematic illustration of a therapeutic substance deliverydevice that includes a disinfection assembly and is configured to engagewith two prefilled therapeutic substance reservoirs, the reservoirsbeing shown outside the therapeutic substance delivery device, inaccordance with some applications of the present invention;

FIG. 2B is a schematic illustration of the therapeutic substancedelivery device of FIG. 2A with the prefilled therapeutic substancereservoirs shown engaged with the therapeutic substance delivery device,in accordance with some applications of the present invention;

FIG. 2C is a schematic illustration of the therapeutic substancedelivery device of FIGS. 2A-B showing establishment of fluidcommunication by penetration of the reservoirs with respective needles,in accordance with some applications of the present invention;

FIG. 2D is a schematic illustration of a therapeutic substance deliverydevice that includes two disinfection assemblies and is configured toengage with two prefilled therapeutic substance reservoirs, thereservoirs being shown engaged with the therapeutic substance deliverydevice, in accordance with some applications of the present invention;

FIG. 3A is a schematic illustration of a therapeutic substance deliverydevice that includes a disinfection assembly and two needles, and isconfigured to engage with a prefilled therapeutic substance reservoir,the reservoir being shown outside the therapeutic substance deliverydevice, in accordance with some applications of the present invention;

FIG. 3B is a schematic illustration of the therapeutic substancedelivery device of FIG. 3A with the prefilled therapeutic substancereservoir engaged with the therapeutic substance delivery device, inaccordance with some applications of the present invention;

FIG. 3C is a schematic illustration of the therapeutic substancedelivery device of FIGS. 3A-B, showing establishment of fluidcommunication by penetration of the reservoir with the two needles, inaccordance with some applications of the present invention;

FIG. 4A is a schematic illustrations of a therapeutic substance deliverydevice that includes a disinfection assembly, and a sensor disposedwithin a disinfection chamber;

FIG. 4B is a graph showing a model that may be used to determinedisinfection time based on measurements taken by the sensor of FIG. 4A,in accordance with some applications of the present invention; and

FIG. 5 is a schematic illustration of a therapeutic substance deliverydevice that includes a disinfection assembly, showing a current metercoupled to the control circuitry, in accordance with some applicationsof the present invention.

DETAILED DESCRIPTION

Reference is now made to FIGS. 1A-C, which are schematic illustrationsof a therapeutic substance delivery device 20 configured to engage witha therapeutic substance reservoir 32, e.g., a prefilled therapeuticsubstance reservoir 32, in accordance with some applications of thepresent invention. Within therapeutic substance delivery device 20 is asterile fluid path 22 for delivering therapeutic substance to a subject.Sterile fluid path 22 has a needle 26 at an upstream end 24 of sterilefluid path 22, and an injection assembly 30 at a downstream end 28 ofsterile fluid path 22. Therapeutic substance delivery device 20 andprefilled therapeutic substance reservoir 32 are configured to engagewith one another, such as is shown by arrow 33 in FIG. 1A, e.g.,reservoir 32 is configured to be inserted into therapeutic substancedelivery device 20. When therapeutic substance delivery device 20 andreservoir 32 are engaged with one another, such as is shown in FIG. 1B,a sealed disinfection chamber 34 is defined between sterile fluid path22 and reservoir 32. While therapeutic substance delivery device 20 andreservoir 32 are typically sterile, disinfection chamber 34 is (a)initially non-sterile, and (b) typically sealed from further bacteria orvirus penetration. Needle 26 may be driven to penetrate disinfectionchamber 34 and subsequently reservoir 32 when therapeutic substancedelivery device 20 and reservoir 32 are engaged with one another, suchthat fluid communication is established between reservoir 32 and sterilefluid path 22, such as is shown in FIG. 1C.

Disposed within therapeutic substance delivery device 20 is adisinfection assembly 36 that disinfects disinfection chamber 34 priorto needle 26 penetrating disinfection chamber 34. Typically, controlcircuitry 38 activates disinfection assembly 36, terminates theactivation of disinfection assembly 36 after disinfection chamber 34 hasbeen disinfected, and then drives needle 26 to penetrate disinfectionchamber 34 and subsequently reservoir 32. Once fluid communication isestablished between reservoir 32 and sterile fluid path 22, controlcircuitry 38 drives a pump assembly 40 to draw therapeutic substancefrom reservoir 32 and deliver it to the subject via injection assembly30.

Typically, in order to decrease the amount of time spent disinfecting,disinfection chamber 34 is small. For example, a total surface area ofdisinfection chamber 34 may be at least 1 mm2 and/or less than 400 mm2.Disinfection can therefore typically occur within 5 minutes, e.g.,within 10 seconds. Control circuitry 38 is typically configured toterminate the activation of disinfection assembly 36 within 5 minutes,e.g., within 10 seconds, after activating disinfection assembly 36.

Local disinfection of the engagement site between reservoir 32 andtherapeutic substance delivery device 20 from inside the delivery deviceallows for (a) engagement of reservoir 32 and therapeutic substancedelivery device 20 to occur substantially prior to therapeutic substancedelivery device 20 being used to deliver the therapeutic substance to asubject, while (b) disinfection of the engagement site may not occuruntil moments before delivery of the therapeutic substance. For example,prefilled therapeutic substance reservoir 32 may be inserted intotherapeutic substance delivery device 20 up to 3 years prior totherapeutic substance delivery device 20 being used for delivery of atherapeutic substance.

For some applications, once attached to a subject, a user control may beused to activate control circuitry 38. In response to activation by theuser control, control circuitry 38 (a) activates disinfection assembly36 such that disinfection chamber 34 is disinfected, (b) terminates theactivation of disinfection assembly 36 within 5 minutes after activatingdisinfection assembly 36, and (c) drives needle 26 to penetratedisinfection chamber 34 within 10 seconds after terminating theactivation of disinfection assembly 36. Thus, disinfecting ofdisinfection chamber 34 typically occurs within 5 minutes prior topenetrating disinfection chamber 34 and then reservoir 32 with needle26.

Additionally, local disinfection of the engagement site that (a) occursinside the delivery device after the engagement, and (b) is activated bycontrol circuitry 38, reduces, in a way that is automated and integratedinto therapeutic substance delivery device 20, a risk of potentiallyharmful bacteria or viruses coming in to contact with the therapeuticsubstance. Typically, reservoir 32 does not have to be disinfected priorto engagement with therapeutic substance delivery device 20, e.g., byswabbing reservoir 32 with alcohol, nor does engagement of the reservoirand the therapeutic substance delivery device have to occur while thereservoir and the fluid path are contained within a sterile environment.

For some applications, the apparatus may be packaged for commercial salewith therapeutic substance delivery device 20 and prefilled therapeuticsubstance reservoir 32 already engaged with one another and configuredfor use typically within 3 years. Typically, therapeutic substances usedin patch pumps have a shelf-life of up to around 3 years. Thus, thedisinfecting of disinfection chamber 34 within 5 minutes prior to needle26 penetrating disinfection chamber 34 may occur up to 3 years, e.g., atleast 1 month, e.g., at least 6 months, following engagement oftherapeutic substance reservoir 32 with therapeutic substance deliverydevice 20.

For some applications, a first disinfecting of disinfection chamber 34may occur prior to therapeutic substance delivery device 20 beingpackaged for commercial sale, which helps to reduce bacterial growthwithin disinfection chamber during shelf-life. Thus, the disinfecting ofdisinfection chamber 34 that occurs within 5 minutes prior to needle 26penetrating disinfection chamber 34 and then reservoir 32 may be atleast a second disinfecting, e.g., occurring at least 1 month (e.g., atleast 6 months, e.g., up to 3 years) following the first disinfecting ofdisinfection chamber 34 that occurs prior to therapeutic substancedelivery device 20 being packaged for commercial sale. For someapplications, disinfecting disinfection chamber 34 may also occurintermittently during the shelf-life of therapeutic substance deliverydevice 20, i.e., at least one time between the first disinfecting ofdisinfection chamber 34 (prior to commercial packaging) and the seconddisinfecting of disinfection chamber 34 (within 5 minutes prior topenetration by needle 26).

For some applications, therapeutic substance delivery device 20 may bepackaged for commercial sale along with prefilled therapeutic substancereservoir 32, but without therapeutic substance delivery device 20 andreservoir 32 being already engaged. Alternatively, therapeutic substancedelivery device 20 may be packaged for commercial sale on its own,without prefilled therapeutic substance reservoir 32.

For some applications, disinfection assembly 36 is an ultravioletradiation source 37 (FIG. 1B), e.g., an ultraviolet light emitting diode(UV LED), that is configured to irradiate disinfection chamber 34 byemitting ultraviolet radiation 42 inside disinfection chamber 34. Forsome applications, the UV LED may be mounted within therapeuticsubstance delivery device 20 such that only the actual diode of the UVLED is inside disinfection chamber 34, while other electronic componentsassociated with the UV LED are outside of disinfection chamber 34 andconnected to control circuitry 38. For example, there may be a smallhole in disinfection chamber 34 through which the UV LED or associatedelectronic components are sealably disposed. Ultraviolet radiationsource 37 is typically configured to emit ultraviolet radiation 42 at awavelength of at least 100 nm and/or less than 400 nm. Ultravioletradiation source 37 may be configured to emit ultraviolet radiation 42at a plurality of wavelengths.

For some applications, at least one surface of disinfection chamber 34,such as surface 46, is a reflective surface configured to reflectultraviolet radiation 42. For example, surface 46 may be configured toreflect at least 10% of ultraviolet radiation 42. For some applications,reflective surface 46 may be expanded polytetrafluoroethylene (ePTFE) oraluminum. Surface 46 being reflective and disinfection chamber 34 beingsmall, as described hereinabove, may independently and/or in combinationallow for the disinfection assembly 36 to operate on low power.Typically, ultraviolet radiation source 37 is configured to emitultraviolet radiation 42 at a power level of less than 200 mW.

Reference is now made to FIG. 1D, which is a schematic illustration oftherapeutic substance delivery device 20 showing a reflective surface 46a within a disinfection chamber, in accordance with some applications ofthe present invention. For some applications, the reflective surface ofdisinfection chamber 34 may be a curved reflective surface 46 a thatfocuses the ultraviolet radiation to a designated area A that is, forexample, within a 3 mm distance D of where needle 26 penetratestherapeutic substance reservoir 32. For example, curved surface 46 a maybe configured to reflect at least 10% of ultraviolet radiation 42 towarddesignated area A. Focusing the ultraviolet radiation to a small areasurrounding the penetration point on therapeutic substance reservoir 32increases the efficacy of the disinfection around the penetration point.For some applications, reflective surface 46 a may be expandedpolytetrafluoroethylene (ePTFE) or aluminum. For some applications, morethan one surface of disinfection chamber 34 may be reflective, forexample, surface 46 and surface 46 a may both be configured to reflectultraviolet radiation 42.

For some applications, disinfection assembly 36 is a heat source. Whenactivated by control circuitry 38, the heat source disinfectsdisinfection chamber 34 by heating disinfection chamber 34 to atemperature of at least 40 degrees Celsius and/or less than 300 degreesCelsius, e.g., 70 degrees Celsius. Alternatively or additionally,disinfection assembly 36 is a disinfectant fluid reservoir that containsdisinfectant fluid. When activated by control circuitry 38, thedisinfectant fluid assembly releases the disinfectant fluid, e.g.,sprays the disinfectant fluid, from the disinfectant fluid reservoirinto disinfection chamber 34.

Reference is now made to FIGS. 2A-C, which are schematic illustrationsof therapeutic substance delivery device 20 configured to engage with afirst prefilled therapeutic substance reservoir 50 and a secondprefilled therapeutic substance reservoir 52, in accordance with someapplications of the present invention. For some applications,therapeutic substance delivery device 20 has a first sterile fluid path54 and a second sterile fluid path 56. At an upstream end 58 of firststerile fluid path 54 is a first needle 60, and at an upstream end 62 ofsecond sterile fluid path 56 is a second needle 64. First sterile fluidpath 54 and second sterile fluid path 56 share a common downstream end66, at which is disposed injection assembly 30. FIG. 2A shows firsttherapeutic substance reservoir 50 and second therapeutic substancereservoir 52 ready to be inserted into therapeutic substance deliverydevice 20. When first prefilled therapeutic substance reservoir 50 andsecond prefilled therapeutic substance reservoir 52 are engaged withtherapeutic substance delivery device 20, such as is shown in FIG. 2B,(a) a first disinfection chamber 68 is defined between first sterilefluid path 54 and first reservoir 50, and (b) a second disinfectionchamber 70 is defined between second sterile fluid path 56 and secondreservoir 52.

First needle 60 and second needle 64 are driven by control circuitry 38to penetrate first disinfection chamber 68 and second disinfectionchamber 70 respectively, and subsequently first reservoir 50 and secondreservoir 52 respectively, such as is shown in FIG. 2C. Thereby a firstfluid communication is established between first sterile fluid path 54and first reservoir 50, and a second fluid communication is establishedbetween second sterile fluid path 56 and second reservoir 52. Whenactivated by control circuitry 38, disinfection assembly 36, e.g.,ultraviolet radiation source 37, (a) disinfects first disinfectionchamber 68 prior to first needle 60 penetrating first disinfectionchamber 68, and (b) disinfects second disinfection chamber 70 prior tosecond needle 64 penetrating second disinfection chamber 70. Forexample, ultraviolet radiation source 37 may emit ultraviolet radiation42 through respective walls of first disinfection chamber 68 and seconddisinfection chamber 70. Within 5 minutes after activation, controlcircuitry 38 terminates the activation of disinfection assembly 36, andsubsequently drives first needle 60 and second needle 64 to respectivelypenetrate first disinfection chamber 68 and second disinfection chamber70 within 10 seconds after terminating the activation of disinfectionassembly 36.

Typically, two valves are used to control fluid communication betweenthe respective reservoirs and injection assembly 30. For example, afirst sterile fluid path valve 72 may be disposed between first needle60 and injection assembly 30 to control fluid communication betweenfirst reservoir 50 and injection assembly 30, and a second sterile fluidpath valve 74 may be disposed between second needle 64 and injectionassembly 30 to control fluid communication between second reservoir 52and injection assembly 30.

Reference is now made to FIG. 2D, which is a schematic illustration oftherapeutic substance delivery device 20 with two disinfectionassemblies. For some applications, instead of using one disinfectionassembly to disinfect both disinfection chambers 68 and 70, a firstdisinfection assembly 76, e.g., a first ultraviolet radiation source 77,disinfects first disinfection chamber 68, and a second disinfectionassembly 78, e.g., a second ultraviolet radiation source 79, disinfectssecond disinfection chamber 70. Control circuitry 38 may activate thefirst and second disinfection assemblies simultaneously or independentlyof each other. When first disinfection assembly 76 and seconddisinfection assembly 78 are activated independently, control circuitry38 (a) drives first needle 60 to penetrate first disinfection chamber 68within 10 seconds after terminating the activation of first disinfectionassembly 76, and (b) drives second needle 64 to penetrate seconddisinfection chamber 70 within 10 seconds after terminating theactivation of second disinfection assembly 78. All features ofdisinfection assembly 36 described hereinabove with reference to FIGS.1A-C and FIGS. 2A-C may apply to first disinfection assembly 76 andsecond disinfection assembly 78.

Reference is now made to FIGS. 3A-C, which are schematic illustrationsof therapeutic substance delivery device 20 configured to engage withprefilled therapeutic substance reservoir 32, in accordance with someapplications of the present invention. For some applications, toincrease the rate of flow of the therapeutic substance, more than oneneedle may be used to establish fluid communication between reservoir 32and sterile fluid path 22. For example, a first needle 80 and a secondneedle 82 may be disposed at upstream end 24 of sterile fluid path 22.Control circuitry 38 activates disinfection assembly 36, e.g.,ultraviolet radiation source 37, to disinfect disinfection chamber 34(FIG. 3B), terminates the activation of disinfection assembly 36 within5 minutes, and subsequently drives first needle 80 and second needle 82to penetrate disinfection chamber 34 and subsequently reservoir 32 (FIG.3C) within 10 seconds after terminating the activation of disinfectionassembly 36. Fluid communication is thereby established via first needle80 and second needle 82.

Reference is now made to FIGS. 4A-B. FIG. 4A is a schematic illustrationof therapeutic substance delivery device 20 showing a sensor 84, e.g.,an ultraviolet sensor, disposed within disinfection chamber 34, and FIG.4B is a graph showing a model that may be used to determine disinfectiontime based on measurements taken by sensor 84, in accordance with someapplications of the present invention. Different UV LED's may emit UVradiation at different intensities; therefore, in order to improveefficiency and efficacy of the disinfection the inventors have realizedthat it is useful for control circuitry 38 to receive an indication ofthe UV intensity within disinfection chamber 34 after activation of theUV LED. Thus, for some applications, in order to improve efficiency andefficacy of the disinfection, control circuitry 38 of therapeuticsubstance delivery device 20 uses a closed-loop feedback system todetermine how long disinfection assembly 36, e.g., ultraviolet radiationsource 37, should be active for, i.e., an amount of time betweenactivation of disinfection assembly 36 and termination of disinfectionassembly 36.

For some applications, after activation of disinfection assembly 36,e.g., ultraviolet radiation source 37, sensor 84 measures the intensityof the ultraviolet radiation within disinfection chamber 34. Controlcircuitry 38 receives the value of the measured UV intensity and, basedon the measured UV intensity, (i) determines a disinfection time and(ii) terminates the irradiation of disinfection chamber 34 at thedetermined time. For some applications, control circuitry 38 maydetermine the disinfection time by using a formula or a look-up table.After termination of the activation of disinfection assembly 36, controlcircuitry 38 drives needle 26 to penetrate disinfection chamber 34 andsubsequently reservoir 32, as described hereinabove. In the exampleshown in FIG. 4B, arrow 86 points to a position on the graph indicatinga value of the measured UV intensity. Arrow 88 points to a correspondingvalue of the determined disinfection time, after which control circuitry38 will terminate the irradiation of disinfection chamber 34. Asdescribed hereinabove termination of the activation of disinfectionassembly 36 typically occurs within 5 minutes, e.g., within 10 seconds,after activating disinfection assembly 36.

For some applications, disinfection assembly 36 may be a heat source, asdescribed hereinabove. Sensor 84 may be a temperature sensor thatmeasures a temperature of disinfection chamber 34 after activation ofthe heat source. Control circuitry 38 receives the measured temperaturevalue from the temperature sensor and, based on the measured temperaturevalue, (i) determines a disinfection time, e.g., by using a formula or alook-up table, and (ii) terminates the heat source at the determinedtime. After termination of activation of the heat source, controlcircuitry 38 drives needle 26 to penetrate disinfection chamber 34 andsubsequently reservoir 32, as described hereinabove.

Reference is now made to FIG. 5, which is a schematic illustration oftherapeutic substance delivery device 20 showing a current meter 90coupled to control circuitry 38, in accordance with some applications ofthe present invention. For some applications, measuring the currentrunning through the UV LED may be indicative of the UV radiation withindisinfection chamber 34. Current meter 90 may measure the currentindicative of the UV radiation within disinfection chamber 34, e.g.,current meter 90 may measure the current going through a resistor withincontrol circuitry 38 that is indicative of the UV radiation withindisinfection chamber 34. After measuring the current indicative of theUV intensity within disinfection chamber 34, control circuitry 38determines a disinfection time, e.g., by using a formula or a look-uptable, and terminates the activation of ultraviolet radiation source 37after the determined time. After termination of disinfection assembly36, control circuitry 38 drives needle 26 to penetrate disinfectionchamber 34 and subsequently reservoir 32, as described hereinabove.

Similarly, for some applications, such as when disinfection assembly 36is a heat source, measuring the current running through the heat sourcemay be indicative of the temperature of disinfection chamber 34. Currentmeter 90 may measure the current indicative of the temperature ofdisinfection chamber 34, e.g., current meter 90 may measure the currentgoing through a resistor within control circuitry 38 that is indicativeof the temperature of disinfection chamber 34. After measuring thecurrent indicative of the temperature of disinfection chamber 34,control circuitry 38 determines a disinfection time, e.g., by using aformula or a look-up table, and terminates the activation of the heatsource at the determined time. After termination of the heat source,control circuitry 38 drives needle 26 to penetrate disinfection chamber34 and subsequently reservoir 32, as described hereinabove.

It is noted that therapeutic substance reservoir 32 is describedhereinabove, for some applications, as being a prefilled therapeuticsubstance reservoir 32. For example, a user may purchase therapeuticsubstance reservoir 32 already filled with a particular therapeuticsubstance. Alternatively, the user may purchase therapeutic substancereservoir 32 empty, and subsequently the user may fill the therapeuticsubstance reservoir.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

The invention claimed is:
 1. A method comprising: using a disinfectionassembly disposed within a therapeutic substance delivery device,disinfecting a disinfection chamber that is defined between (i) aprefilled therapeutic substance reservoir and (ii) a sterile fluid pathdisposed within the therapeutic substance delivery device, the sterilefluid path comprising a needle at an upstream end of the sterile fluidpath and an injection assembly at a downstream end of the sterile fluidpath; and penetrating the disinfection chamber and then the reservoirwith the needle, the disinfecting occurring (a) subsequently to theprefilled therapeutic substance reservoir being engaged with thetherapeutic substance delivery device and (b) prior to the penetratingof the disinfection chamber and then the reservoir with the needle. 2.The method according to claim 1, wherein the step of disinfecting thedisinfection chamber is performed following a user of the therapeuticsubstance delivery device engaging the prefilled therapeutic substancereservoir with the therapeutic substance delivery device, wherein thedisinfection chamber is defined when the prefilled therapeutic substancereservoir becomes engaged with the therapeutic substance deliverydevice.
 3. The method according to claim 1, wherein the step ofdisinfecting the disinfection chamber is performed following a user ofthe therapeutic substance delivery device removing the therapeuticsubstance delivery device from commercial packaging, wherein theprefilled therapeutic substance reservoir and the therapeutic substancedelivery device are engaged with one another inside the commercialpackaging.
 4. The method according to claim 1, wherein disinfecting thedisinfection chamber comprises activating the disinfection assembly andsubsequently terminating the activation of the disinfection assembly,and wherein penetrating the disinfection chamber comprises penetratingthe disinfection chamber within 10 seconds after terminating theactivation of the disinfection assembly.
 5. The method according toclaim 1, wherein disinfecting the disinfection chamber comprisesactivating the disinfection assembly and terminating activation of thedisinfection assembly within 5 minutes after activating the disinfectionassembly.
 6. The method according to claim 1, wherein disinfecting thedisinfection chamber comprises irradiating the disinfection chamber withultraviolet radiation.
 7. The method according to claim 6, whereinirradiating the disinfection chamber comprises irradiating thedisinfection chamber with ultraviolet radiation at a power level of1-200 mW.
 8. The method according to claim 6, wherein irradiating thedisinfection chamber comprises irradiating the disinfection chamber withultraviolet radiation at a wavelength of 100-400 nm.
 9. The methodaccording to claim 6, wherein irradiating the disinfection chambercomprises irradiating the disinfection chamber with ultraviolet lightusing an ultraviolet light emitting diode.
 10. The method according toclaim 6, further comprising: subsequently to irradiating thedisinfection chamber with the ultraviolet light, measuring a valueindicative of intensity of the ultraviolet radiation within thedisinfection chamber; and terminating the irradiation of thedisinfection chamber at a time determined based on the measured value.11. The method according to claim 10, wherein measuring the valueindicative of intensity of the ultraviolet radiation comprises measuringthe intensity of the ultraviolet radiation within the disinfectionchamber using an ultraviolet sensor disposed within the disinfectionchamber.
 12. The method according to claim 10, wherein (a) irradiatingthe disinfection chamber with ultraviolet radiation comprises activatingan ultraviolet light emitting diode (UV LED) and (b) measuring the valueindicative of intensity of the ultraviolet radiation comprises measuringa current input to the UV LED.
 13. The method according to claim 1,wherein disinfecting the disinfection chamber comprises heating thedisinfection chamber.
 14. The method according to claim 13, whereinheating the disinfection chamber comprises heating the disinfectionchamber to a temperature of 40-300 degrees Celsius.
 15. The methodaccording to claim 1, wherein disinfecting the disinfection chambercomprises releasing a disinfectant fluid into the disinfection chamber.16. The method according to claim 1, wherein disinfecting thedisinfection chamber comprises disinfecting the disinfection chamberwithin 5 minutes prior to penetrating the disinfection chamber andsubsequently the reservoir with the needle.
 17. The method according toclaim 16, wherein disinfecting the disinfection chamber comprisesdisinfecting the disinfection chamber at least 1 month followingengagement of the prefilled therapeutic substance reservoir with thetherapeutic substance delivery device.
 18. The method according to claim17, wherein disinfecting the disinfection chamber comprises disinfectingthe disinfection chamber at least 6 months following engagement of theprefilled therapeutic substance reservoir with the therapeutic substancedelivery device.
 19. The method according to claim 16, wherein thedisinfecting of the disinfection chamber is at least a seconddisinfecting of the disinfection chamber, a first disinfecting of thedisinfection chamber occurring prior to the therapeutic substancedelivery device being packaged for commercial sale.
 20. The methodaccording to claim 19, further comprising disinfecting the disinfectionchamber at least one time between the first disinfecting of thedisinfection chamber and the at least a second disinfecting of thedisinfection chamber.